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WT1 immunotherapeutic anti-cancer treatment in high-risk multiple myeloma: clinical benefits with Galinpepimut-S

Results from the phase II study of WT1 first-in-class immunotherapeutic anti-cancer treatment in multiple myeloma patients following autologous stem cell transplantation ( ASCT ) were presented.
Initial results have indicated for the first time a meaningful clinical benefit among high-risk multiple myeloma patients, who typically relapse within a year of ASCT.
Galinpepimut-S, was licensed from Memorial Sloan Kettering Cancer Center ( MSK ) and is an innovative WT1 targeted immunotherapeutic, with the potential to treat multiple tumor types.

The study, which enrolled a total of 19 patients, has demonstrated 86% actuarial overall survival of 18 months, with 17 of the 18 evaluable patients still alive today.
Of the evaluable patient population, 15 had high-risk cytogenetics, as well as additional unfavorable clinical characteristics, which together typically result in low progression-free survival rates that do not exceed 12-15 months following ASCT.

The results compare favorably with an unmatched cohort of multiple myeloma patients with high-risk cytogenetics published by the MD Anderson Cancer Center, demonstrating a near doubling of the progression-free survival rate at 18 months, with a corresponding relative 43% increase in overall survival in a landmark comparison.

The median overall survival of the phase II study has not been reached, nor has the median progression-free survival, however the latter is poised to be greater than 18 months.

Treatments for high-risk multiple myeloma have remained a clinical challenge. Now, for the first time, Galinpepimut-S has provided strong indication of a meaningful clinical benefit, following autotransplantation in patients with high-risk multiple myeloma, particularly those with an adverse cytogenetic profile.
Reserachers have previously demonstrated that Wilms' tumor antigen 1 ( WT1 ) is selectively overexpressed on malignant plasma cells and immunotherapeutic strategies targeting this antigen could improve key outcomes in patients with multiple myeloma.

Galinpepimut-S has demonstrated positive phase II results in acute myeloid leukemia and malignant pleural mesothelioma in the past year, with phase III programs poised to commence in these tumor types.

WT1 immunotherapeutic anti-cancer treatment ( generically designated as Galinpepimut-S ) is a cancer immunotherapy being developed to target hematologic cancers and solid tumors, including acute myeloid leukemia ( AML ), mesothelioma ( MPM ), multiple myeloma, ovarian cancer, and multiple other cancers.
The WT1 antigen is a transcription factor that is not generally expressed in normal adult cells, but appears in a large number of cancers, as well as in certain cancer stem cells.
WT1 has been ranked by the National Cancer Institute ( NCI ) as the Number 1 target for cancer immunotherapy.
While WT1 has not been druggable by traditional approaches, it can be targeted by the immune system.
Specifically, a number of different peptide sequences from the WT1 antigen have been identified as immunogenic and capable of stimulating cytotoxic T-cells that can target and kill WT1-expressing cancer cells.
Studies also have shown that WT1 does not provoke tolerization and that patients' T-cells can remain reactive to the antigen over time.

Galinpepimut-S comprises four modified heteroclitic peptide chains that induce a strong innate immune response ( CD4+/CD8+ T-cells ) against the WT1 antigen.
Galinpepimut-S is administered in combination with an adjuvant and an immune modulator to improve the immune response to the target.
Based on its mechanism and the accumulating evidence of activity in mid-stage trials, galinpepimut-S may have the potential to complement currently available therapies by destroying residual tumor cells of cancers in remission and providing ongoing immune surveillance for recurrent tumors.
Overall, Galinpepimut-S could target over 20 cancers that over-express WT1, many of which are associated with relapse rates of up to 80% or more, as seen in patients with acute myeloid leukemia and mesothelioma. ( Xagena )

Source: Sellas, 2016